title: 6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase.
abstract: N-3-hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development.
authors.affiliation: Center for Drug Design, University of Minnesota, 516 Delaware St SE, Minneapolis, MN 55455, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.forename: Kasthuraiah
authors.initials: K
authors.lastname: Maddali
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dreis
authors.forename: Yuk Y
authors.initials: YY
authors.lastname: Sham
authors.forename: Robert
authors.initials: R
authors.lastname: Vince
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D019428:HIV Integrase Inhibitors; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D019427:HIV Integrase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C030986:pyrimidine